PPARs-Orchestrated Metabolic Homeostasis in the Adipose Tissue

Abstract

It has been more than three decades since peroxisome proliferator-activated receptors (PPARs) were first discovered. Many investigations have revealed the central regulators of PPARs in lipid and glucose homeostasis in response to different nutrient conditions. PPARs have attracted much attention due to their ability to improve metabolic syndromes, and they have also been proposed as classical drug targets for the treatment of hyperlipidemia and type 2 diabetes (T2D) mellitus. In parallel, adipose tissue is known to play a unique role in the pathogenesis of insulin resistance and metabolic syndromes due to its ability to “safely” store lipids and secrete cytokines that regulate whole-body metabolism. Adipose tissue relies on a complex and subtle network of transcription factors to maintain its normal physiological function, by coordinating various molecular events, among which PPARs play distinctive and indispensable roles in adipocyte differentiation, lipid metabolism, adipokine secretion, and insulin sensitivity. In this review, we discuss the characteristics of PPARs with special emphasis on the roles of the different isotypes in adipocyte biology.

Lemon Balm and Corn Silk Extracts Mitigate High-Fat Diet-Induced Obesity in Mice

“…To investigate whether M-LB/CS prevents the diet-induced obesity through modulating lipid metabolism in the adipose tissue, qPCR analysis was conducted ( Table 2 ). As expected, HFD significantly increased mRNA levels of C/EBPα, C/EBPβ, PPARγ, and SREBP-1c, which are representative genes associated with lipogenesis and adipocyte differentiation [ 23 , 24 ]. However, various combination ratios of M-LB/CS significantly blocked the induction of C/EBPα, C/EBPβ, PPARγ, and SREBP-1c.…”

“…The magnitude of the reductions by 1:1, 1:2, 2:1, and 4:1 combination ratios of M-LB/CS was greater than that caused by single herbal extract alone. On the contrary, HFD significantly inhibited specific mRNAs involved in lipolysis and energy expenditure (e.g., PPARα and UCP2) [ 23 , 25 ]. Moreover, reciprocal changes on mRNA expression of leptin and adiponectin were shown in mice fed an HFD.…”

“…PPARs belong type II nuclear receptor superfamily and are transcription factors, which govern nutrient and energy metabolisms after binding of lipophilic ligands [ 23 ]. Three PPAR subtypes (i.e., PPARα, PPARβ/δ, and PPARγ) share structural similarity, but differ in pathophysiological function via inducing different set of genes.…”

“…Three PPAR subtypes (i.e., PPARα, PPARβ/δ, and PPARγ) share structural similarity, but differ in pathophysiological function via inducing different set of genes. For instance, PPARα, in the adipose tissue, promotes lipolysis by regulating essential genes correlated with triglyceride hydrolysis (e.g., lipase), fatty acid uptake (e.g., cluster of differentiation 36 and carnitine palmitoyltransferase), β-oxidation (e.g., acyl-CoA oxidase), and thermogenesis (e.g., UCP) [ 23 , 25 ]. On the contrary, PPARγ facilitates preadipocytes maturation (e.g., C/EBPs) and lipogenesis (e.g., SREBP-1) in the adipose tissue [ 23 , 24 ].…”

“…For instance, PPARα, in the adipose tissue, promotes lipolysis by regulating essential genes correlated with triglyceride hydrolysis (e.g., lipase), fatty acid uptake (e.g., cluster of differentiation 36 and carnitine palmitoyltransferase), β-oxidation (e.g., acyl-CoA oxidase), and thermogenesis (e.g., UCP) [ 23 , 25 ]. On the contrary, PPARγ facilitates preadipocytes maturation (e.g., C/EBPs) and lipogenesis (e.g., SREBP-1) in the adipose tissue [ 23 , 24 ]. Interestingly, studies from in vitro ligand binding assay and reporter gene assay, harboring PPAR response element, indicated that LBE is capable of binding and transactivating three canonical PPARs [ 12 , 60 ].…”